Our overall research program of a series of psychophysical and neurophysiological experiments to examine the specific features of pain perception and the neuronal substrate involved in the processing of inputs activated by noxious stimuli. Psychophysical experiments employ a paradigm based on signal detection theory. In one study, the changes in bias and discriminability associated with an analgesic effect are assessed. In other experiments using the same paradigm, the effects of electrical stimuli applied to the body surface, to peripheral nerves and to the spinal cord on the perception of experimentally induced noxious stimuli are determined. The neurophysiological studies are directed towards determining: (1) the action of various descending systems on the responses of spinothalamic neurons to naturally evoked peripheral stimuli, and (2) the segmental mechanisms by which these effects are mediated. Emphasis is placed upon the action of the systems arising in the brainstem.